Dataset Information

Promoter competition and Polycomb Response Elements govern transvection efficiency between co-regulated engrailed and invected genes in Drosophila.

ABSTRACT: Transvection is a phenomenon where gene regulatory elements interact between different chromosomes, adding an additional layer of regulatory control beyond traditional cis-interactions. Although transvection effects have been characterized for many individual genes in Drosophila, it remains unclear how trans-interactions occur among multiple co-regulated genes where enhancers are shared. Here we demonstrate that transvection is supported at the engrailed-invected (en-inv) locus, where transcription of the two developmental patterning genes is coordinated by common enhancers. Our data show that the presence of the en promoter in cis to the enhancers prevents trans-activation of inv, but removal of this promoter enables robust transvection, demonstrating competition between heterologous promoters in trans. We also find that local Polycomb Response Elements (PREs) enhance transvection reliability but are not strictly required for trans-activation. Furthermore, our analysis reveals that transvection at this locus is developmentally regulated, occurring efficiently in third instar larval tissues and late-stage embryos but not in early embryonic stages. Finally, we show that en-inv transvection can be reconstituted using transgenic constructs at an ectopic chromosomal location where it produces a striking reciprocal expression pattern between en in cis and inv in trans, suggesting that these enhancers can choose to activate one promoter or the other in a stochastic manner.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE308802 | GEO | 2025/09/25

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Cohesin is crucial for proper chromosome segregation, but also regulates gene transcription and organism development by poorly understood mechanisms. We find that in Drosophila, cohesin functionally interacts with Polycomb group (PcG) silencing proteins at both silenced and active genes. Cohesin unexpectedly facilitates binding of Polycomb Repressive Complex 1 (PRC1) to many active genes. In contrast, cohesin and PRC1 binding are mutually antagonistic at silenced genes. PRC1 depletion decreases phosphorylated RNA polymerase and mRNA at many active genes, but increases them at silenced genes. Cohesin also facilitates long-range interactions between Polycomb Response Elements in the invected-engrailed gene complex where it represses transcription. These multiple distinct cohesin-PcG interactions reveal a previously unrecognized role for PRC1 in facilitating productive gene transcription, and provide new insights into how cohesin and PRC1 control development. ChIP-chip of cohesin, Polycomb group proteins, and RNA Polymerase II was performed in whole wing imaginal discs in developing wing imaginal disc, revealing that cohesin and Polycomb Repressive Complex 1 (PRC1) components co-bind with cohesin proteins at active genes. We then measured cohesin, Pc, and H3K27me3 separately in anterior and posterior wing imaginal discs and compared their binding at the invected-engrailed complex, which is silenced in the anterior disc, and expressed in its posterior. This confirmed that cohesin and PRC1 (Pc) co-bind at inv-en in its active state, and H3K27me3 and PRC1 (Pc) co-target inv-en in its silenced state. Comparison of binding between Pc-RJ and Pc-VP was performed, and revealed that Pc-VP is subject to epitope masking specifically at active genes. Finally, we measured cohesin and Pc binding in Drosophila ML-DmBG3-c2 cells, and found that they co-bind active genes in this cell line in as well as in wing imaginal discs. ChIP-chip of cohesin subunit Rad21 after PRC1 component Ph depletion, and ChIP-chip of PRC1 subunit Pc after Rad21 RNAi depletion, revealed that these two complexes affect one another's binding. Finally, ChIP-chip of Rpb3 (representing total Pol II) and Ser2P-Pol II (representing elongating Pol II) after PRC1 component Ph depletion revealed that PRC1 restrains entry of non-phosphorylated Pol II into gene bodies.

Project description:Gene expression differences between species are driven by both cis and trans effects. Whereas cis effects on gene expression are due to nearby genetic variants, trans effects are due to distal genetic variants that affect diffusible elements such as transcription factors. However, as previous studies have mostly assessed the impacts of cis and trans effects at the gene level, how cis and trans effects differentially impact regulatory elements such as enhancers and promoters remains poorly understood. Here, we used massively parallel reporter assays to directly measure cis and trans effects between human and mouse embryonic stem cells at thousands of individual regulatory elements, including enhancers as well as promoters of both protein-coding and long non-coding RNA genes. Our approach revealed that cis effects are widespread across regulatory elements, and the strongest cis effects are associated with the disruption of motifs recognized by strong transcriptional activators. Conversely, we found that trans effects are rare but stronger in enhancers than promoters, and can be attributed to a subset of transcription factors that are differentially expressed between human and mouse. While previous gene-based studies have found extensive co-occurrence of cis and trans effects in opposite directions that stabilize gene expression between species—or compensatory cis-trans effects—we find that cis-trans compensation is uncommon within individual regulatory elements. Moreover, regulatory elements that do show compensatory cis-trans effects are often less redundant than regulatory elements lacking compensatory cis-trans effects. Thus, our results are consistent with a model wherein compensatory cis-trans effects occur more often through crosstalk between multiple redundant regulatory elements than within a single individual regulatory element. Together, these results indicate that studying the evolution of individual regulatory elements is pivotal to understand the tempo and mode of gene expression evolution.

Dataset Information

Promoter competition and Polycomb Response Elements govern transvection efficiency between co-regulated engrailed and invected genes in Drosophila.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets